Figure 4.
Selective depletion of senescent cells in the BM niche. (A) Schematic of the experiment. Aged p16-3MR mice and C57Bl/6 mice were treated with 25 mg/kg of GCV for 5 days followed by a recovery period of 7 days. (B) Number of MSCs and in C57Bl/6 or p16-3MR mice after treatment with GCV. (C) Frequency of TMRMhi MSCs in C57Bl/6 or p16-3MR mice treated with GCV. (D) p16-3MR mice were first treated with GCV as before and after the 7-day recovery period they were treated with LPS 0.5 mg/kg; they were killed at 16 hours. Flow cytometry was used to determine cell numbers of LSKs, LS-Ks, and MPPs. (E) Flow cytometry was used to measure the frequency of TMRMhi LSKs, LKs, and MPPs. (F) Seahorse metabolic flux analysis was used to measure OCR in aged p16-3MR and C57Bl/6 mice after GCV treatment followed by LPS or vehicle control. Change in OCR compared with extracellular acidification rate (ECAR) is shown. (G) Changes in basal and maximal respiration. ∗P < .05, ∗∗P < .01 using the Mann-Whitney U test or two-way analysis of variance. Con, vehicle control; ns, not significant.

Selective depletion of senescent cells in the BM niche. (A) Schematic of the experiment. Aged p16-3MR mice and C57Bl/6 mice were treated with 25 mg/kg of GCV for 5 days followed by a recovery period of 7 days. (B) Number of MSCs and in C57Bl/6 or p16-3MR mice after treatment with GCV. (C) Frequency of TMRMhi MSCs in C57Bl/6 or p16-3MR mice treated with GCV. (D) p16-3MR mice were first treated with GCV as before and after the 7-day recovery period they were treated with LPS 0.5 mg/kg; they were killed at 16 hours. Flow cytometry was used to determine cell numbers of LSKs, LS-Ks, and MPPs. (E) Flow cytometry was used to measure the frequency of TMRMhi LSKs, LKs, and MPPs. (F) Seahorse metabolic flux analysis was used to measure OCR in aged p16-3MR and C57Bl/6 mice after GCV treatment followed by LPS or vehicle control. Change in OCR compared with extracellular acidification rate (ECAR) is shown. (G) Changes in basal and maximal respiration. ∗P < .05, ∗∗P < .01 using the Mann-Whitney U test or two-way analysis of variance. Con, vehicle control; ns, not significant.

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